Objective: Spontaneous intracranial hypotension (SIH), which is often caused by a spinal cerebrospinal fluid leak, is an important cause of disabling headaches. Many patients report devastating changes in their quality of life because of their symptoms. This study aimed to evaluate the impact of SIH on patients’ social/ working life and health-related quality of life (HRQoL). Methods: We included consecutive patients with proven SIH treated at our institution from January 2013 to May 2020. Patients were contacted and asked to complete the 15D questionnaire for the collection of HRQoL data and to provide additional information on their social life status. Results: Of 112 patients, 79 (70.5%) returned the questionnaire and were included in the analysis. Of those, 69 were treated surgically (87.3%), and 10 were managed non-operatively (12.7%). Twenty-five (31.6%) patients reported a severe impact on their partnership, 32 (41.5%) reported a moderate or severe impact on their social life. Forty (54.8%) patients reported sick leave for more than 3 months. The mean 15D score was 0.890 (± 0.114) and significantly impaired compared to an age- and sex-matched general population (p = 0.001), despite treatment. Patients with residual SIH-symptoms (36, 45.6%) had significantly impaired HRQoL compared to those without any residual symptoms (41, 51.9%) (p < 0.001). Conclusion: SIH had a notable impact on the patients’ social life and HRQoL. It caused long periods of incapacity for work, and is therefore, associated with high economic costs. Although all patients were appropriately treated, reduced HRQoL persisted after treatment, underlining the chronic character of this disease.

Well-defined risk factors for cerebrospinal fluid leakage (CSFL) after intradural spine surgery are scarce in the literature. The aim of the present study was to identify patient- and surgery-related risk factors and the incidence of CSFL. For the present retrospective cohort study, we identified consecutive patients who had undergone intradural spine surgery between 2009 and 2021 at our department. The primary endpoint was the incidence of clinically or radiologically proven CSFL. The effects of the clinical and surgical factors on the occurrence of CSFL were analyzed. A total of 375 patients (60.3% women; mean age, 54 ± 16.5 years) were included. Of the 375 patients, 30 (8%) had experienced postoperative CSFL and, thus, a significantly greater risk of wound healing disorders (odds ratio [OR], 24.9; 95% confidence interval [CI], 9.3-66.7) and surgical site infections (OR, 8.4; 95% CI, 2.6-27.7; P < 0.01 for each). No patient-related factors were associated with the development of CSFL. Previous surgery at the index level correlated significantly with the occurrence of postoperative CSFL (OR, 2.76; 95% CI, 1.1-6.8; P = 0.03) on multivariate analysis. Furthermore, patients with intradural tumors tended to have a greater risk of CSFL (OR, 2.3; 95% CI, 0.9-5.8; P = 0.07). Surgery-related factors did not influence the occurrence of CSFL. Surgery on the thoracic spine had resulted in a significantly lower postoperative CSFL rate compared with surgery on the cervical or lumbar spine (OR, -2.5; 95% CI, 1.3-4.9; P = 0.02). Our study found no modifiable risk factors for preventing CSFL after intradural spine surgery. Patients with previous surgery at the index level had a greater risk of CSFL. The occurrence of CSFL resulted in significantly more wound healing disorders and surgical site infections, necessitating further therapy.

Mutations in RNA binding proteins (RBPs) and in genes regulating autophagy are frequent causes of familial amyotrophic lateral sclerosis (fALS). The P56S mutation in vesicle-associated membrane protein-associated protein B (VAPB) leads to fALS (ALS8) and spinal muscular atrophy (SMA). While VAPB is primarily involved in the unfolded protein response (UPR), vesicular trafficking and in initial steps of the autophagy pathway, the effect of mutant P56S-VAPB on autophagy regulation in connection with RBP homeostasis has not been explored yet. Examining the muscle biopsy of our index ALS8 patient of European origin revealed globular accumulations of VAPB aggregates co-localised with autophagy markers LC3 and p62 in partially atrophic and atrophic muscle fibres. In line with this skin fibroblasts obtained from the same patient showed accumulation of P56S-VAPB aggregates together with LC3 and p62. Detailed investigations of autophagic flux in cell culture models revealed that P56S-VAPB alters both initial and late steps of the autophagy pathway. Accordingly, electron microscopy complemented with live cell imaging highlighted the impaired fusion of accumulated autophagosomes with lysosomes in cells expressing P56S-VAPB. Consistent with these observations, neuropathological studies of brain and spinal cord of P56S-VAPB transgenic mice revealed signs of neurodegeneration associated with altered protein quality control and defective autophagy. Autophagy and RBP homeostasis are interdependent, as demonstrated by the cytoplasmic mis-localisation of several RBPs including pTDP-43, FUS, Matrin 3 which often sequestered with P56S-VAPB aggregates both in cell culture and in the muscle biopsy of the ALS8 patient. Further confirming the notion that aggregation of the RBPs proceeds through the stress granule (SG) pathway, we found persistent G3BP- and TIAR1-positive SGs in P56S-VAPB expressing cells as well as in the ALS8 patient muscle biopsy. We conclude that P56S-VAPB-ALS8 involves a cohesive pathomechanism of aberrant RBP homeostasis together with dysfunctional autophagy.

Data on intraoperative neurophysiological monitoring (IOM) during spinal meningioma (SM) surgery are scarce. The aim of this study was to assess the role of IOM and its impact on post-operative functional outcome. Eighty-six consecutive surgically treated SM patients were included. We assessed pre and post-operative Modified McCormick Scale (mMCS), radiological and histopathological data and IOM findings. Degree of cord compression was associated with preoperative mMCS and existence of motor or sensory deficits (p < 0.001). IOM was used in 51 (59.3%) patients (IOM-group). Median pre and post-operative mMCS was II and I, respectively (p < 0.001). Fifty-seven (66.3%) patients showed an improvement of at least one grade in the mMCS one year after surgery. In the IOM group, only one patient had worsened neurological status, and this was correctly predicted by alterations in evoked potentials. Analysis of both groups found no significantly better neurological outcome in the IOM group, but IOM led to changes in surgical strategy in complex cases. Resection of SM is safe and leads to improved neurological outcome in most cases. Both complication and tumor recurrence rates were low. We recommend the use of IOM in surgically challenging cases, such as completely ossified or large ventrolateral SM.

The authors present an illustrative technical note on microsurgical resection of ventrolateral completely ossified spinal meningiomas (OSMs) and a literature review of the surgical management of calcified spinal meningiomas or OSMs. These tumors are surgically demanding due to their solid consistency, especially when in a ventrolateral location with dislocation of the spinal cord. A challenging case with significant thoracic cord compression and displacement is described. Due to the firm consistency and the ventrolateral localization of the meningioma, a piecemeal resection was necessary. This could have resulted in a free-floating tumor remnant adherent to the spinal cord, impeding safe tumor resection. To avoid such a remnant, an anchoring burr hole was drilled at the border between the spinal cord and the adamantine tumor mass. Then, a microdissector was placed within the anchoring burr hole and the tumor was gently pulled laterally while drilling away the medial parts of the ossified tumor. This procedure was repeated until separation of the tumor from the spinal cord was possible and a gross-total resection (Simpson grade II) was manageable. Throughout the procedure, continuous intraoperative neurophysiological monitoring was performed.

Although orthostatic headache is the hallmark symptom of spontaneous intracranial hypotension (SIH), patients can present with a wide range of different complaints and thereby pose a diagnostic challenge for clinicians. Our aim was to describe and group the different symptoms associated with SIH and their course over time. We retrospectively surveyed consecutive patients diagnosed and treated for SIH at our institution from January 2013 to May 2020 with a specifically designed questionnaire to find out about their symptomatology and its course. Of 112 eligible patients, 79 (70.5%) returned the questionnaire and were included in the analysis. Of those, 67 (84.8%) reported initial orthostatic headaches, whereas 12 (15.2%) denied having this initial symptom. All except one (98.7%) patients reported additional symptoms: most frequently cephalic pressure (69.6%), neck pain (68.4%), auditory disturbances (59.5%), nausea (57%), visual disturbances (40.5%), gait disturbance (20.3%), confusion (10.1%) or sensorimotor deficits (21.5%). Fifty-seven (72.2%) patients reported a development of the initial symptoms predominantly in the first three months after symptom onset. Age and sex were not associated with the symptomatology or its course (p > 0.1). Although characteristic of SIH, a relevant amount of patients present without orthostatic headaches. In addition, SIH can manifest with non-orthostatic headaches at disease onset or during the course of the disease. Most patients report a wide range of associated complaints. A high degree of suspicion is crucial for an early diagnosis and targeted treatment.